Human genetic factors associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity

Human Genomics, Год журнала: 2020, Номер 14(1)

Опубликована: Окт. 22, 2020

Abstract Background The emergence of the novel coronavirus in Wuhan, Hubei Province, China, December 2019 marked synchronization world to a peculiar clock that is counting infected cases and deaths instead hours minutes. pandemic, highly transmissible severe acute respiratory syndrome 2 (SARS-CoV-2) has indeed caused considerable morbidity mortality drastically changed our everyday lives. As we continue become acquainted with seventh known infect species, number its characteristics keep surprising us. Among those wide spectrum clinical manifestations resulting disease (COVID-19), which ranges from asymptomatic or mildly symptomatic infections pneumonia, failure, death. Main body Data, now patient populations, are beginning accumulate on human genetic factors may contribute observed diversified severity. Therefore, deemed it prudent review associations between specific variants severity susceptibility infection have been reported literature date (at time writing this article early August 2020 updates mid-September). With work, hope (i) assist fast-paced biomedical research efforts combat virus by critically summarizing current knowledge potential role host genetics, (ii) help guide genetics genomics towards candidate gene warrant further investigation larger studies. We found determinants differing COVID-19 predominantly include components immune response virus, while SARS-CoV-2 mostly entail genes related initial stages (i.e., binding cell surface receptor entry). Conclusion Elucidating would allow for stratification individuals according risk so at high be prioritized immunization, example, if when safe effective vaccines developed. Our enhanced understanding underlying biological mechanisms could also personalized therapeutics. Such already provide clues explain, least part, epidemiologic observations regarding typically more benign course older males children, respectively.

Язык: Английский

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Host genetic factors determining COVID-19 susceptibility and severity

EBioMedicine, Год журнала: 2021, Номер 72, С. 103629 - 103629

Опубликована: Окт. 1, 2021

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) poses an unprecedented challenge to humanity. SARS-CoV-2 infections range from asymptomatic severe courses of with acute respiratory distress syndrome (ARDS), multiorgan involvement and death. Risk factors for disease severity include older age, male sex, increased BMI pre-existing comorbidities. Ethnicity is also relevant susceptibility severity. Host genetic predisposition now increasingly recognized whole genome candidate gene association studies regarding have been performed. Several common rare variants in genes related inflammation or immune responses identified. We summarize research on host genetics compile associated discuss that should be investigated further understand such associations provide insights pathogenesis, risk classification, therapy response, precision medicine, drug repurposing.

Язык: Английский

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Genetics Insight for COVID-19 Susceptibility and Severity: A Review

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Апрель 1, 2021

Coronavirus disease (COVID-19) presents a broad spectrum of clinical manifestations ranging from an asymptomatic to severe course. The host genetic background influence on the susceptibility and outcome multiples infectious diseases has been previously reported. Herein, we aimed describe relevant identified variants those potentially related inter-individual variability COVID-19 and/or severity considering physiopathological pathway HLA-A*25:01 , - B*15:27 -B*46:01 -C*01:02 -C*07:29 alleles have associated with susceptibility; while HLA-A*02:02 -B*15:03 -C*12:03 as low-risk alleles. Variants in cytokine genes such IL1B IL1R1 IL1RN IL6 IL17A FCGR2A TNF could be storm, complications (e.g., venous thrombosis). Several ACE2 TMPRSS2 affecting expression receptors risk factors. Finally, two GWAS loci 3p21.31 ( LZTFL1 SLC6A20 CCR9 FYCO1 CXCR6 XCR1 ) 9q34.2 ABO severity. Heterogeneous results association were observed. mechanism risk-genes studies different populations are still warranted.

Язык: Английский

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Association between HLA genotypes and COVID-19 susceptibility, severity and progression: a comprehensive review of the literature

European journal of medical research, Год журнала: 2021, Номер 26(1)

Опубликована: Авг. 3, 2021

The COVID-19 pandemic has markedly impacted on cultural, political, and economic structures all over the world. Several aspects of its pathogenesis related clinical consequences have not yet been elucidated. Infection rates, as well morbidity mortality differed within countries. It is intriguing for scientists to understand how patient genetics may influence outcome condition, clarify which could be variability SARS-CoV-2 disease. We reviewed studies exploring role human leukocyte antigens (HLA) genotypes individual responses infection and/or progression, discussing also contribution immunological patterns MHC-related. In March 2021, main online databases were accessed. All articles that investigated possible association between HLA polymorphisms with susceptibility, severity progression considered. Although both genetic environmental factors are certainly expected susceptibility or protection individuals, can infection. crucial played by molecules in immune response, especially through pathogen-derived peptide presentation, huge molecular alleles populations responsible different rates patients following

Язык: Английский

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Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19

iScience, Год журнала: 2021, Номер 24(4), С. 102322 - 102322

Опубликована: Март 19, 2021

The established risk factors of coronavirus disease 2019 (COVID-19) are advanced age, male sex, and comorbidities, but they do not fully explain the wide spectrum manifestations. Genetic implicated in host antiviral response provide for novel insights into its pathogenesis.We performed an in-depth genetic analysis chromosome 21 exploiting genome-wide association study data, including 6,406 individuals hospitalized COVID-19 902,088 controls with European ancestry from Host Genetics Initiative. We found that five single nucleotide polymorphisms within TMPRSS2 near MX1 gene show associations severe COVID-19. minor alleles (SNPs) correlated a reduced developing high level expression blood.Our findings demonstrate can influence different clinical presentations could be potential therapeutic target.

Язык: Английский

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Genetic and epigenetic factors associated with increased severity of Covid‐19

Cell Biology International, Год журнала: 2021, Номер 45(6), С. 1158 - 1174

Опубликована: Фев. 16, 2021

Since December 2019, a new form of severe acute respiratory syndrome (SARS) from novel strain coronavirus (SARS 2 [SARS-CoV-2]) has been spreading worldwide. The disease caused by SARS-CoV-2 was named Covid-19 and declared as pandemic the World Health Organization in March 2020. Clinical symptoms range common cold to more defined pneumonia, hypoxia, distress. In next stage, can become critical with failure, sepsis, septic shock, and/or multiorgan failure. Outcomes indicate large gaps between male-female young-elder groups. Several theories have proposed explain variations, such gender, age, comorbidity, genetic factors. It is likely that mixture nongenetic factors interplays virus host genetics determines severity outcome. this review, we aimed summarize current literature terms potential epigenetic associated increased Covid-19. studies indicated variants entry mechanism-related (angiotensin-converting enzymes, transmembrane serine protease-2, furin) innate immune response-related genes (interferons [IFNs], interleukins, toll-like receptors), human leukocyte antigen, ABO, 3p21.31, 9q34.2 loci are determinants related severity. Epigenetic mechanisms also affect outcomes regulating IFN signaling, angiotensin-converting enzyme-2, immunity-related particularly escape X chromosome inactivation. Enhanced understanding viral interactions for improved prognostic tools innovative therapeutics.

Язык: Английский

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HLA variation and antigen presentation in COVID-19 and SARS-CoV-2 infection

Current Opinion in Immunology, Год журнала: 2022, Номер 76, С. 102178 - 102178

Опубликована: Март 25, 2022

The extraordinary variation of the human leukocyte antigen (HLA) molecules is critical for diversifying presentation to T cells. Coupled with rise novel strains and rapidly evolving immune evasion by SARS-CoV-2 proteins, HLA-mediated immunity in COVID-19 critically important but far from being fully understood. A growing number studies have found association HLA variants different outcomes that genotypes associate differential responses against SARS-CoV-2. Prediction shown mutations multiple viral strains, most concentrated Spike protein, affect affinity between these mutant peptides molecules. Understanding impact this on T-cell comprehending immunogenic mechanisms both natural vaccine development.

Язык: Английский

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HLA-A*11:01:01:01, HLA-C*12:02:02:01-HLA-B*52:01:02:02, Age and Sex Are Associated With Severity of Japanese COVID-19 With Respiratory Failure

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Апрель 22, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing disease 2019 (COVID-19) was announced as an outbreak by World Health Organization (WHO) in January 2020 and a pandemic March 2020. The majority of infected individuals have experienced no or only mild symptoms, ranging from fully asymptomatic cases to pneumonic disease. However, minority develop severe symptoms. objective this study identify susceptible HLA alleles clinical markers that can be used risk prediction model for early identification COVID-19 among hospitalized patients. A total 137 patients with (mCOVID-19) 53 (sCOVID-19) were recruited Center Hospital National Global Medicine (NCGM), Tokyo, Japan period February–August High-resolution sequencing-based typing eight genes performed using next-generation sequencing. In association studies, HLA-A*11:01:01:01 [P c = 0.013, OR 2.26 (1.27–3.91)] HLA-C*12:02:02:01-HLA-B*52:01:01:02 0.020, 2.25 (1.24–3.92)] found significantly associated severity COVID-19. After multivariate analysis controlling other confounding factors comorbidities, 3.34E-03, 3.41 (1.50–7.73)], age at diagnosis 1.29E-02, 1.04 (1.01–1.07)] sex birth 8.88E-03, 2.92 (1.31–6.54)] remained significant. area under curve utilizing HLA-A*11:01:01:01, diagnosis, 0.772, sensitivity 0.715 specificity 0.717. To best our knowledge, is first article describes associations 4-field (highest) resolution level. Early potential sCOVID-19 could help clinicians prioritize medical utility decrease mortality

Язык: Английский

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Genetic polymorphisms associated with susceptibility to COVID-19 disease and severity: A systematic review and meta-analysis

PLoS ONE, Год журнала: 2022, Номер 17(7), С. e0270627 - e0270627

Опубликована: Июль 6, 2022

Although advanced age and presence of comorbidities significantly impact the variation observed in clinical symptoms COVID-19, it has been suggested that genetic variants may also be involved disease. Thus, aim this study was to perform a systematic review with meta-analysis literature identify polymorphisms are likely contribute COVID-19 pathogenesis. Pubmed, Embase GWAS Catalog repositories were systematically searched retrieve articles investigated associations between COVID-19. For analyzed 3 or more studies, pooled OR 95% CI calculated using random fixed effect models Stata Software. Sixty-four eligible included review. In total, 8 7 candidate genes 74 alleles HLA loci studies. The HLA-A*30 CCR5 rs333Del associated protection against infection, while APOE rs429358C allele risk for Regarding severity, HLA-A*33, ACE1 Ins, TMPRSS2 rs12329760T severe forms, HLA-B*38, HLA-C*6, ApoE forms conclusion, ApoE, ACE1, TMPRSS2, CCR5, appear susceptibility and/or severity

Язык: Английский

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Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

Gene, Год журнала: 2022, Номер 844, С. 146790 - 146790

Опубликована: Авг. 17, 2022

Язык: Английский

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